8jl3: Difference between revisions
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== Disease == | == Disease == | ||
[https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Sanfilippo syndrome type C | [https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Retinitis pigmentosa;Sanfilippo syndrome type C. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.<ref>PMID:16960811</ref> <ref>PMID:17033958</ref> <ref>PMID:19823584</ref> <ref>PMID:20650889</ref> | [https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.<ref>PMID:16960811</ref> <ref>PMID:17033958</ref> <ref>PMID:19823584</ref> <ref>PMID:20650889</ref> | ||
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== Publication Abstract from PubMed == | |||
Lysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT), whose dysfunction leads to lysosomal storage diseases. The mechanism by which HGSNAT, the sole non-hydrolase enzyme in HS degradation, brings cytosolic acetyl-coenzyme A (Ac-CoA) and lysosomal HS together for N-acyltransferase reactions remains unclear. Here, we present cryogenic-electron microscopy structures of HGSNAT alone, complexed with Ac-CoA and with acetylated products. These structures explain that Ac-CoA binding from the cytosolic side causes dimeric HGSNAT to form a transmembrane tunnel. Within this tunnel, catalytic histidine and asparagine approach the lumen and instigate the transfer of the acetyl group from Ac-CoA to the glucosamine group of HS. Our study unveils a transmembrane acetylation mechanism that may help advance therapeutic strategies targeting lysosomal storage diseases. | |||
Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.,Xu R, Ning Y, Ren F, Gu C, Zhu Z, Pan X, Pshezhetsky AV, Ge J, Yu J Nat Struct Mol Biol. 2024 Oct;31(10):1502-1508. doi: 10.1038/s41594-024-01315-5. , Epub 2024 May 20. PMID:38769387<ref>PMID:38769387</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||
